Plasma Leptin Concentrations in Relation to Sick Euthyroid Syndrome in Elderly Patients with Nonthyroidal Illnesses

Abstract

Background: Leptin, the ob gene product, seems to be involved in regulating energy expenditure in humans, but its role in the pathophysiology of the energy imbalance in chronically ill patients is largely unknown. Objective: To evaluate plasma leptin concentrations and thyroid function in elderly patients with nonthyroidal illnesses (NTI). Methods: Sixty-four NTI elderly patients (75.0 ± 6.3 years, 27 males and 37 females) and 21 age- and sex-matched healthy controls (73.0 ± 5.5 years, 9 males and 12 females) were enrolled in the study. In all subjects tri-iodothyronine (T₃), thyroxine (T₄), reverse T₃ (rT₃), free T₃ (fT₃), free T₄ (fT₄), TSH, and plasma leptin concentrations were measured. Nutritional status was also evaluated in all subjects studied by the measurement of body mass index (BMI), lymphocytes, serum iron, hemoglobin, plasma albumin, transferrin and total cholesterol. Results: The data on thyroid hormones enabled us to identify three groups: group A, subjects (15 patients) with T₃ and fT₃ levels comparable to those of controls; group B, subjects (25 patients) with T₃ and fT₃ levels lower than controls and rT₃ levels comparable to those of controls; group C, subjects (24 patients) with T₃ and fT₃ levels lower than those of controls and high rT₃ levels. The patients of group C showed lower plasma leptin levels than the controls, 6.6 (5.5–14.2) and 16.3 (7.2–23.7) ng/ml (median with interquartile range in parentheses, p < 0.05), respectively. Females also showed higher plasma leptin levels than males in the controls, group A and group B, but not in group C. Moreover, plasma leptin concentrations were directly correlated to BMI in all the groups studied, while a negative correlation between leptin and rT₃ was detectable in group C (r = –0.44, p < 0.05), also after adjusting for BMI and sex. Conclusions: The concurrence of modifications in plasma leptin and thyroid hormones concentrations found in elderly NTI patients with a sick euthyroid syndrome could reflect a particular neuroendocrine status, leading to a reduction in the catabolic processes in the course of chronic diseases.

Overweight, Waist Circumference, Age, Gender, and Insulin Resistance as Risk Factors for Hyperleptinemia

“…The average concentrations in older subjects with normal weight are similar to those observed in other studies for controls Ͼ60 years of age (10,52,53). The mean numbers coincide with investigations that show that the older subjects present higher serum leptin levels than young adults (20,31,50,52).…”

“…There is scientific evidence showing that leptin is involved in the initiation of puberty, pregnancy, breast‐feeding, immune system regulation, inflammatory processes, respiratory function, sex hormones, growth hormone, and thyroid hormones, in addition to bone tissue metabolism, septic processes, hematopoiesis, cachexia, and others (6, 7, 8, 9, 10, 11, 12, 13, 14, 15).…”

Euthyroid Sick Syndrome

“…Serum leptin levels decrease during fasting as well as in elderly patients with the euthyroid sick syndrome, leading to subsequent decrease in TSH levels (27). These changes likely serve as an adaptive mechanism to reduce catabolic process and energy expenditure in the setting of acute illness (9,27,106). Increased hypothalamic D2 activity as well as increased Triac production also have been reported to directly decrease TSH production, similar to what has been observed in the pituitary (14).…”

“…Leptin has been reported to directly regulate TRH production, and leptin and TSH levels are directly related to each other (15,54,75). Serum leptin levels decrease during fasting as well as in elderly patients with the euthyroid sick syndrome, leading to subsequent decrease in TSH levels (27). These changes likely serve as an adaptive mechanism to reduce catabolic process and energy expenditure in the setting of acute illness (9,27,106).…”

Thyroid hormones modulate the endocrine and autocrine/paracrine actions of leptin on thyrotropin secretion

“…The same may be occurring in some cases of euthyroid sick syndrome. It has been reported that among elderly patients with chronic non-thyroidal illnesses, those who presented low serum free thyroxine (T4) and free T3 -as well as high reverse T3 -also had low concentrations of serum leptin (Corsonello et al 2000). In addition, hypothyroid patients may show decreased serum leptin (Valcavi et al 1996), although there is some disagreement in published reports (Zimmermann-Belsing et al 2003) and so far a consistent relationship between serum concentrations of leptin and thyroid hormone has not been established.…”